Answer to Question #124991 in Biochemistry for K Ganesh

Question

In aqueous solution, almost all D-glucose molecules are in the pyranose form. Other aldoses have a greater proportion of molecules in the open-chain form. D-Glucose may have evolved to be the predominant hexose because it is less likely than its isomers to react with and damage cellular proteins. Explain why D-glucose reacts less than other aldoses with the amino groups of proteins.

Answer 1

Compared to other hexose sugars, glucose has a low tendency to non-specifically react with the amino groups of proteins. This reaction (glycosylation) destroys the function of many enzymes. The low rate of glycosylation is due to glucose's preference for the less reactive cyclic isomer.

Glucose is the most widely used aldohexose in most living organisms. An explanation for this is that glucose has a lower tendency than other aldohexoses to react non-specifically with the amine groups of proteins. This reaction that is called glycation impairs the function of many proteins, e.g., in glycated hemoglobin. Glucose's low rate of glycation can be attributed to its having a more stable cyclic form compared to other aldohexoses, which means that it spends less time than they do in its reactive open-chain form. The reason for glucose having the most stable cyclic form of all the aldohexoses is that its hydroxy groups (with the exception of the hydroxy group on anomeric carbon of d-glucose) are in the equatorial position. Glucose is the most abundant natural monosaccharide because it is less glycated with proteins than other monosaccharides. Another hypothesis is that glucose, being the only D-aldohexose which has all five hydroxy substituents in the equatorial position in the form of beta-D-glucose, is more readily accessible to chemical reactions, for instance, for esterification or acetal formation. For this reason, D-glucose is also a highly preferred building block in natural polysaccharides (glycans). Polysaccharides which are composed solely of glucose are termed glucans.